A Spin-1 Representation for Dual-Funnel Energy Landscapes
Justin E. Elenewski, Kirill Velizhanin, Michael P. Zwolak
The interconversion between left- and right-handed helical folds of a polypeptide defines a dual-funneled free energy landscape. In this context, the funnel minima are connected through a continuum of unfolded conformations, evocative of the classical helix-coil transition. Physical intuition and recent conjectures suggest that this landscape can be mapped by assigning a left- or right-handed helical state to each residue. We explore this possibility using all-atom replica exchange molecular dynamics and an Ising--like model, demonstrating that the energy landscape architecture is at odds with a two-state picture. A three-state model - left, right, and unstructured - can account for most key intermediates during chiral interconversion. Competing folds and excited conformational states still impose limitations on the scope of this approach. However, the improvement is stark: Moving from a two-state to a three-state model decreases the fit error from 1.6 kT to 0.3 kT along the left-to-right interconversion pathway.
, Velizhanin, K.
and Zwolak, M.
A Spin-1 Representation for Dual-Funnel Energy Landscapes, The Journal of Chemical Physics, [online], https://doi.org/10.1063/1.5036677
(Accessed December 10, 2023)